The present program deals with the mechanism of limited proteolysis and its role in physiological regulation. The following projects will be pursued in the current granting period: 1. Limited proteolysis of zymogens and other proteins of known structure in order to define more precisely the conformational requirements of the substrate for specific peptide bond cleavage. 2. The mode of action of bovine enterokinase, the role of divalent cations, and the possible presence of an enterokinase precursor. 3. The physiological role and mode of action of proteases of mast cells. 4. Limited proteolysis of precursors of secretory proteins ("signal peptides") of the hen oviduct. 5. The role of proteolytic enzymes in fertilization of sea urchin eggs. 6. Protease action and protein structure, including the sequence determination of blood coagulation factors IX and X and the catalytic subunit of protein kinase. 7. Methodological developments of sequence analysis including the further development of microsequencing techniques.